The new methods of phosphodiester synthesis, (R1O)(R2O)P(O)OH, developed by the principal investigator will be applied to the synthesis of: (1) Natural phospholipids; (2) Unnatural phospholipids; (3) Phospholipid analogs. The main target structures within these categories are: (1) Cardiolipins (or diphosphatidylglycerol of heart muscle mitochondria), phosphatidyl-diglycerides, and phosphosphingolipids (phosphomyelin). (2) Phospholiposteroids, phospholiponucleosides, and phospholipo-drugs. In this class, the phosphorylated diglyceride (phosphatidic acid) moiety of natural lipids is retained, but the second moiety is replaced by cholesterol, testosterone (at C17-OH), pregnenolone (at C3-OH), etc., or by a nucleoside, or by a pharmacodynamic alcohol. (3) Alkylphosphorylcholines. In this class the lipophilic diglyceride moiety of natural lecithins is replaced by lipophilic groups derived from steroids and other structures, while the choline cation of the lecithins is retained. The objectives of the research are: (1) To study the mechanism of membrane transport of uncharged and ionic substances by modifications of the phospholipid component. (II) To make lipid vesicles able to fuse with the membranes of specific target cells to deliver drugs to those particular cells. The methods proposed for the syntheses are described in: F. Ramirez, et. al., Tetrahedron, 33, 599 (1977); Synthesis, 483 (1976) and (1977). Available techniques for studies on model phospholipid bilayers, vesicles and Pressman liquid barriers will be employed.